Mouse intestinal cryptdins exhibit circadian oscillation

Abstract

The innate immunity utilizes a plethora of antibacterial polypeptides, known as defensins, to combat ingested bacteria. Mouse enteric defensins (cryptdins) are produced and secreted constitutively but are overexpressed in instances of infection and/or inflammation. Our objective was to determine whether the biological clock plays a role in cryptdin expression under healthy conditions. Analysis of cryptdin 1 and cryptdin 4 expression in the ileum and jejunum of the small intestine of FVB/N mice around the circadian cycle revealed oscillation that peaked at the end of the dark phase. To eliminate the possibility that cryptdin oscillation stems from food intake, we analyzed cryptdin expression under fasting conditions and found oscillation but with a 3 h phase-shift. Comparison of cryptdin expression in two mouse strains (C57BL/6 vs. FVB/N) revealed higher levels in C57BL/6, a mouse strain that is highly susceptible to enteric infection, due, most likely, to impaired cryptdin maturation. The results of this study indicate the involvement of the biological clock in regulating cryptdin expression in the small intestine and reinforce the capacity of food to act as a zeitgeber (synchronizer). With the assumption of similar control in humans, our results may imply that defensin expression peaks during the day.

Late-night-dinner is associated with poor glycemic control in people with type 2 diabetes: The KAMOGAWA-DM cohort study

“…Nutrition factors, such as food intake, appetite and digestion, have an effect on circadian patterns [36]. Food intake modulates the circadian rhythms, especially in liver and intestine [37,38] and misalignment of circadian rhythm leads to insulin resistance and diabetes [39,40]. In fact, skipping breakfast, one of the irregular eating, is associated with metabolic syndrome, diabetes and cardiovascular disease [6,7].…”

Clock is important for food and circadian regulation of macronutrient absorption in mice

“…Therefore, Clock is more important than the presence of food in the intestinal lumen in the regulation of intestinal transport proteins. cryptidins ( 62 ) and most of the toll-like receptors ( 13 ) show circadian oscillations in the jejunum. Although we did not do a comprehensive systemic study, our sampling of critical intestinal functional proteins surprisingly revealed that several nutrient transport proteins show circadian expression and their expression is absent in Clk mt/mt .…”

“…Samples were embedded in optimal cutting temperature compound, rapidly frozen in liquid nitrogen, and stored at Ϫ 80°C. Frozen sections were cut with a cryostat (8 by guest, on May 12, 2018 www.jlr.org Downloaded from before or at the time of food availability, whereas Cry1 , Cry2, and Bmal1 levels increased 4 h later. In Clk mt/mt mice, however, these changes were not seen.…”

“…by guest, on May 12, 2018 www.jlr.org Downloaded from absorption might contribute to hyperlipidemia, hyperglycemia, obesity, and metabolic syndrome in Clk mt/mt mice. Food entrainment shifted the expression of different transport proteins to just before or at mealtime.…”

High α‐defensin levels in patients with systemic lupus erythematosus

“…Total RNA was DNAse I-treated using RQ1 DNAse (Promega, Madison, WI) for 2 hr at 37°, as was previously described. 27,28 Then 2 lg of DNAse I-treated RNA was reverse-transcribed using Moloney murine leukaemia virus (MMuLV) reverse transcriptase (Promega) and random hexamers. A 1/20 aliquot of the reaction was then subjected to quantitative real-time PCR using the Sybr Green Master kit (Applied Biosystems) and the ABI Prism 7300 Sequence Detection System (Applied Biosystems).…”